Use of normobaric and hyperbaric oxygen in acute focal cerebral ischemia - a preclinical and clinical review

Abstract

High socioeconomic burden is attributed to acute ischemic stroke, but treatment strategies are still limited. Normobaric (NBO) and hyperbaric oxygen therapy (HBO) were frequently investigated in preclinical studies following acute focal cerebral ischemia with predominantly beneficial effects in different outcome measurements. Best results were achieved in transient cerebral ischemia, starting HBO early after artery occlusion, and by using relatively high pressures. On molecular level, oxygen application leads to blood-brain barrier stabilization, reduction of excitotoxic metabolites, and inhibition of inflammatory processes. Therefore, NBO and HBO appear excessively hopeful in salvaging impaired brain cells during ischemic stroke. However, harmful effects have been noted contributing to damaging properties, for example, vasoconstriction and free oxygen radicals. In the clinical setting, NBO provided positive results in a single clinical trial, but HBO failed to show efficacy in three randomized trials. To date, the translation of numerous evidentiary experimental results into clinical implementation remains open. Recently, oxygen became interesting as an additional therapy to neuroprotective or recanalization drugs to combine positive effects. Further preclinical research is needed exploring interactions between NBO, HBO, and key factors with multiphasic roles in acute damaging and delayed inflammatory processes after cerebral ischemia, for example, matrix-metalloproteinases and hypoxia-inducible factor-1α.